A Study of Atezolizumab Versus Placebo as Adjuvant Therapy in Participants With High-risk Muscle-invasive Bladder Cancer (MIBC) Who Are ctDNA Positive Following Cystectomy

Inclusion Criteria: Inclusion Criteria for the Surveillance Phase: Histologicall [...] e contraception and agreement to refrain from donating eggs Exclusion Criteria: General Medical Exclusion Criteria for the Surveillance Phas [...]

Inclusion Criteria for the Surveillance Phase: Histologically confirmed MIUC (also termed transitional cell carcinoma [TCC]) of the bladder Tumor, nodes, and metastases (TNM) classification (based on American Joint Committee on Cancer [AJCC] Cancer Staging Manual, 8th Edition; Amin et al. 2016) at pa [...] examination of surgical resection specimen as follows: For patientsparticipants treated with prior neoadjuvant chemotherapy (NAC): tumor stage of ypT2-4a or ypN+ and M0. For patientsparticipants who have not received prior NAC: tumor stage of pT2-4a or pN+ and M0 Surgical resection of MIUC of the [...] [...]

Independent Review Facility (IRF)-Assessedassessed DFS Investigator-AssessedINV Disease-Specificspecific Survival (DSS) Investigator-AssessedINV Distant Metastasis-Freefree Survival (DMFS) Time to Confirmed Deterioration of Function and Health Related-related Quality of Life (HRQoL) Percentage of Participants With Adverse Events (AEs)

Investigator-assessed (INV) - Disease-free Survival (DFS)

A Study of Atezolizumab Versus Placebo as Adjuvant Therapy in PatientsParticipants With High-Riskrisk Muscle-Invasiveinvasive Bladder Cancer (MIBC) Who Are ctDNA Positive Following Cystectomy

OsakaThe University of Osaka Hospital

[...] -4a or pN+ and M0 Surgical resection of MIUC of the bladder Patients who have received prior platinum-based NAC. Patients who have not received prior platinum-based NAC, havemust refused, arebe ineligible ("unfit") for cisplatin-based adjuvant chemotherapy, have refused it, or will not receive it based on physicisanphysician's decision. ctDNA assay developed based on tumor tissue spe [...] days prior to randomization, as assessed by the investigator and Independent Review Facility ECOG Performance Status of <= 2 Life expectancy >=12 weeks [...] juvant therapy should not be based on the PD-L1 IHC result. If [...] [...]

Instituto CancerologiaCancerología Medellin; Clinica Las Americas

[...] o have not received prior platinum-based NAC, have refused, or are ineligible ("unfit") for cisplatin-based adjuvant chemotherapy, or will not receive based on physicisan's decision. ctDNA assay developed based on tumor tissue specimen and m [...]

Overall survival (OS) in Participants Who Are ctDNA Positive Within 24 weeks After Cystectomy Investigator-assessed DFS in All Randomized Participants Independent Review Facility (IRF)-Assessed DFS in Primary Analysis Population IRF-Assessed DFS in All Randomized Participants Investigator-Assessed Disease-Specific Survival in Primary Analysis Population Investigator-Assessed Distant Metastasis-Free Survival in Primary Analysis Population Time to Confirmed Deterioration of Function and Health Related Quality of Life (HRQoL) in Primary Analysis Population and in All Randomized Population ctDNA C [...] [...]

Investigator-assessed DFS in Participants Who Are ctDNA Positive Within 24 Weeks of Cystectomy

Time to Deterioration of Function and Health Related Quality of Life (QoLHRQoL) in Primary Analysis Population and in All Randomized Population

[...] domen, and chest no more than 28 days prior to randomization., as assessed by the investigator ECOG Performance Status of <= 2 Life expectancy >=12 weeks Adequate hematologic and end-organ function, investigator decision For women of childbearing potential: agreement to remain ab [...] juvant therapy should not be based on the PD-L1 IHC result. If a cap is in effect limiting enrollment of PD-L1 negative patients, this exclusion criterion will not apply. Pregnancy or breastfeeding Positive test for HIV, with the f [...] past HBV infection or resolved HBV infection are eligible. A negative HBV DNA test must [...] [...]

[...] -4a or pN+ and M0 Surgical resection of MIUC of the bladder Patients who have received prior platinum-based NAC. Patients who have not received prior platinum-based NAC, hav [...] igible ("unfit") for cisplatin-based adjuvant chemotherapy. pT2N0 patients who have not received prior platinum-based NAC regardless of cisplatin ineligibility are eligible. ctDNA assay developed based on tumor tissue specimen and mat [...]

[...] er TNM classification (based on AJCC Cancer Staging Manual, 7th8th Edition; EdgeAmin et al. 20102016) at pathological examination of surgical resection specimen [...] llment. Full recovery from cystectomy and enrollment within 1424 weeks following cystectomy. Minimum of 6 weeks must have el [...] positive, defined as the presence of two or more mutations out of the 16 mutations identified based on patient's WES evaluable (ctDNA assay designability) [...] or MRI scan of the pelvis, abdomen, and chest no more than 428 weeksdays prior to randomization. ECOG Performance Status of <= 2 Lif [...] efrain from donating eggs Ge [...]

Overall survival (OS) in Participants Who Are ctDNA Positive Within 2024 weeks After Cystectomy IRFInvestigator-assessed DFS in All Randomized Participants InvestigatorIndependent Review Facility (IRF)-Assessed DFS in Primary Analysis Population InvestigatorIRF-Assessed DFS in All Randomized Participants

IRFInvestigator-assessed DFS in Participants Who Are ctDNA Positive Within 2024 Weeks of Cystectomy

[...] or patients who have not received prior NAC: tumor stage of pT3pT2-4a or pN+ and M0 Surgical resection of MIUC of the bladder [...] eligible ("unfit") for cisplatin-based adjuvant chemotherapy. pT2N0 patients who have not received prior platinum-based NAC regardless of cisplatin ineligibility are eligible. ctDNA assay developed based on tumor tissue specimen and matched normal DNA from blood. Tumor PD-L1 expression per IHC andthat confirmedis diagnosisevaluable of MIUC as documented throughby central testing of a representative tumor tissue specimen. Absence of residual disease and absence of metast [...] [...]